A Study to Investigate the Efficacy and Safety of Bendamustine Compared With Bendamustine+Obinutuzumab (GA101) in Participants With Rituximab-Refractory, Indolent Non-Hodgkin's Lymphoma (GADOLIN)

Genentech

Status and phase: Completed; Phase 3

Conditions: Non-Hodgkin's Lymphoma

Treatments: Drug: Obinutuzumab; Drug: Bendamustine

Study type: Interventional

Funder types: Industry

Identifiers

NCT01059630

2009-015504-25 (EudraCT Number)

GO01297 (Other Identifier)

GAO4753g

Details and patient eligibility

About

This open-label, multicenter, randomized Phase III study will investigate the efficacy, safety, pharmacokinetics and pharmacoeconomics of obinutuzumab (RO5072759, GA101) combined with bendamustine followed by continued obinutuzumab treatment (maintenance monotherapy) compared with bendamustine alone treatment in participants with rituximab-refractory indolent Non-Hodgkin's lymphoma (iNHL). The end of study was defined to when safety follow-up for all patients had been completed (2 years' safety follow-up from last dose).

Enrollment: 413 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• History of histologically documented, B-lymphocyte antigen cluster of differentiation 20 plus (CD20+), iNHL
• Refractory to any previous regimen containing rituximab (defined by participants who did not respond or who progressed during or up to 6 months after treatment with rituximab or a rituximab-containing regimen)
• Previously treated with a maximum of four unique chemotherapy containing treatment regimens
• All participants must have at least one bi-dimensionally measurable lesion (greater than [>]1.5 centimeters (cm) in its largest dimension by computed tomography [CT] scan)

Exclusion criteria

• Prior use of any monoclonal antibody (other than anti-CD20) within 3 months prior to the start of Cycle 1, prior treatment with obinutuzumab was not allowed
• Chemotherapy or other investigational therapy within 28 days prior to the start of Cycle 1
• Prior treatment with bendamustine (within 2 years of the start of Cycle 1)
• Prior allogeneic stem cell transplant
• History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
• History of sensitivity to mannitol
• Central nervous system lymphoma or prior diffuse large B-cell lymphoma (DLBCL), histological evidence of transformation to high grade or diffuse large B-cell lymphoma
• History of other malignancy that could affect compliance with the protocol or interpretation of results
• Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results
• Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) or any major episode of infection requiring treatment with intravenous antibiotics or hospitalization within 4 weeks
• Participants with a history of confirmed progressive multifocal leukoencephalopathy (PML)
• Vaccination with a live vaccine a minimum of 28 days prior to randomization
• Recent major surgery (within 4 weeks), other than for diagnosis
• Presence of positive test results for Hepatitis B surface antigen (HBsAg); antibody to hepatitis B core antigen [anti-HBc]) with detectable viral load (positive hepatitis B virus [HBV] deoxyribo-nucleic acid [DNA]) or Hepatitis C
• Participants with chronic hepatitis B or seropositive occult (HBV) infection
• Participants with seronegative occult HBV infection or past HBV infection (defined as anti-HBc positive and HBV DNA negative) could be eligible if they were willing to be followed according to the protocol for HBV DNA testing
• Participants positive for Hepatitis C virus (HCV) antibody were eligible only if polymerase chain reaction(PCR) was negative for HCV Ribonucleic acid (RNA)
• Known history of human immunodeficiency virus (HIV) seropositive status
• Positive test results for human T-lymphotropic virus type I (HTLV 1) virus in endemic countries
• Women who are pregnant or lactating
• Fertile men or women of childbearing potential unless 1) surgically sterile or 2) using an adequate measure of contraception such as oral contraceptives, intrauterine device, or barrier method of contraception in conjunction with spermicidal jelly
• Ongoing corticosteroid use >30 milligrams per day (mg/day) prednisone or equivalent

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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413 participants in 2 patient groups

Bendamustine Alone

Active Comparator group

Description:

Participants will receive bendamustine 120 milligrams per meter square (mg/m\^2) Intravenous (IV) infusion on Days 1 and 2 of each 28-day cycle for up to six cycles.

Treatment:

Drug: Bendamustine

Obinutuzumab + Bendamustine

Experimental group

Description:

Induction phase: Participants will receive bendamustine 90 mg/m\^2 IV on Days 2 and 3 of Cycle 1 and on Days 1 and 2 of Cycles 2-6 (28-day cycles) for the first 10 participants and on Days 1 and 2 of each 28-day cycle for Cycles 1-6 for remaining participants. Participants will also receive obinutuzumab 1000 mg IV infusion on Days 1, 8, and 15 of Cycle 1; Day 1 of Cycles 2-6. Maintenance phase: Participants with complete response (CR), partial response (PR) or stable response (SD) then will receive obinutuzumab 1000 mg IV infusion every 2 months until disease progression or for up to 2 years (whichever occurs first).

Treatment:

Drug: Bendamustine

Drug: Obinutuzumab